The long-term goal of this career development grant is to obtain and maintain a faculty position and research career in nutrition science with a focus on retinoids in skin and hair and their diseases. The immediate goal is to gain more knowledge about retinoids and their role in skin and hair physiology. The PI will reach these goals thru research, reading, attending seminars, attending and presenting at scientific meetings and publishing findings in the area of retinoids in skin and hair. This research project is focused on the regulation of endogenous retinoid metabolism and signaling during the normal hair cycle. The specific aims are: to establish the localization and precise timing of retinoid metabolism in the hair follicle, sebaceous gland, and stem cells during the hair cycle; to determine if estrogen regulates retinoid metabolism in the cycling hair follicle; and to dissect the specific interactions between endogenous retinoic acid and Wnt signaling during the hair cycle. This is significant as several retinoids may be used to treat skin and hair disorders, but can have toxic side effects. Once we know where endogenous retinoids are being synthesized and how this synthesis is regulated we can begin to explore alternate treatments that have fewer side effects than current exogenous retinoid therapies. In addition, the normal hair cycle is an excellent physiological model of signaling pathways including retinoids. The specific aims of this project will be accomplished thru a series of localization (protein and mRNA) studies of enzymes and binding proteins involved in retinoid metabolism in the hair follicle during natural and induced hair cycles. These studies will be extended by studies in mice. Topically treating mice with estrogen/ant estrogen and analyzing retinoid metabolism by immunohistochemistry will test estrogen regulation. The Lef1/Tcf transgenic mouse model (Tg(Fos-lacZ)34Efu/J; aka TOPGAL) will be treated with retinoids/inhibitors to determine the effects of retinoids in Wnt signaling during the hair cycle. This grant will provide the PI the opportunity to develop into an independent investigator.